New insights into bioactive Ga(III) hydroxyquinolinate complexes from UV-vis, fluorescence and multinuclear high-field NMR studies

Abstract

There is current interest in the anticancer and antimicrobial activities of Ga(III) tris-hydroxyquinolinate complexes, and hence their solution and solid-state chemistry. Here, we have studied the formation, stability and structure of a novel tris-5,7-dibromo-8-hydroxyquinolinate Ga(III) complex [Ga(Br₂-HQ)₃]. Reactions of 5,7-dibromo-8-hydroxyquinoline with Ga(NO)₃ in DMSO were followed using electronic absorption and emission spectroscopy, and revealed the slow but concerted coordination of three chelated ligands, with ligand deprotonation being the apparent rate-limiting step, facilitated by basic Ga(III) hydroxido species. The emissive excited state of [Ga(Br₂-HQ)₃] in DMSO had a short half-life of 1.2 ns, and the fluorescence (550 nm, λ_ex = 400 nm) was characterized by TDDFT calculations as arising from a ligand-centred singlet S1 state. We compared the structures of [Ga(Br₂-HQ)₃] and the clinical tris-hydroxyquinolinate complex [Ga(HQ)₃] using high-field magic-angle-spinning solid-state 1D and 2D 850 MHz and 1 GHz ¹H, ¹³C and ⁷¹Ga NMR spectroscopy. The similarity of their coordination spheres was confirmed by their ⁷¹Ga chemical shifts of 101 and 98 ppm, respectively, and quadrupolar coupling constants of 9.265 MHz and 9.282 MHz. ¹H-¹H 2D NOESY experiments revealed second coordination sphere interactions between an acetic acid solvent molecule and the bound hydroxyquinolinate ligands of [Ga(HQ)₃]·0.5CH₃CO₂H. This finding suggests that carboxylic acids could play a role in modifying the formulation properties of this drug for clinical use.